Low-intensity stimulation drives macrophage efferocytosis via ACSL4 lipid remodeling and CCL9-CCR1 signaling for tendon-bone healing

Science Advances 2026 Open access

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Authors: Juncheng Yao, Y N Wu, Xuan Wang, J K Zhang, Yan Shao, Hao Chen, Haitao Zhang, Hui Li, Jianying Pan, Yuanzhang Zhao, Daozhang Cai, Denghui Xie
+1 more Chun Zeng
DOI: 10.1126/sciadv.adw6666
Cited by: 1
References: 60

Abstract

The mechanisms underlying exercise rehabilitation–induced tendon-bone healing remain unclear. Using a mouse model of anterior cruciate ligament reconstruction, we found that low-intensity mechanical stimulation promoted macrophage M2 polarization, phagocytosis, and efferocytosis at the tendon-bone interface via acyl-CoA synthetase long-chain family member 4 (ACSL4)–mediated lipid metabolism reprogramming. Acsl4 silencing reduced fatty acid oxidation and efferocytosis, impairing exercise rehabilitation–induced tendon-bone healing. Notably, the CCL9-CCR1 axis contributed to bone marrow stromal cell homing following macrophage efferocytosis. In addition, engineered CCL9-expressing exosomes accelerated tendon-bone repair.

Fields of Study & Subjects

Tendon Structure and Treatment Exercise and Physiological Responses Immune cells in cancer

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
28
Pages
eadw6666–eadw6666
Publication date
10 July 2026
Language
EN